The present invention is concerned with an improved antiinflammatory composition and method of treating inflammation which employs a non-steroidal antiinflammatory agent such as piroxicam, or a pharmaceutically acceptable salt thereof (particularly the ethanolamine salt of piroxicam), in combination with N-acetyl-L-methionine or 5'-guanylic acid, or a pharmaceutically acceptable salt thereof. The generic names used here and elsewhere herein are from the USAN and the USP Dictionary of Drug Names, 1961-1981, Griffiths et al., ed., U.S. Pharmacopeial Convention Inc., Rockville, Md., 1984, and/or appear as the primary names in The Merck Index 10th Edition. The alternative systematic name for piroxicam, having the formula ##STR1## is 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (The Merck Index 10th Ed., Monograph No. 7378 and page REG-68). Alternative names for 5'-guanylic acid, having the formula ##STR2## are guanosine 5'-monophosphate and guanine riboside-5-phosphoric acid (Merck Index, 10th Ed.).
Gastrointestinal irritation, including ulcers, is a side effect commonly associated, to one degree or another, with antiinflammatory agents. In many cases, individuals requiring such antiinflammatory treatment are precluded from enjoying the benefits thereof because of their susceptibility to such side effects. The present combination of a non-steroidal antiinflammatory agent with 5'-guanylic acid or N-acetyl-L-methionine permits desirable antiinflammatory therapy while preventing or ameliorating said gastrointestinal irritation or ulcers.
As noted in The Merck Index, 10th Edition, the DL form of N-acetylmethionine finds therapeutic use as a lipotropic, while 5'-guanylic acid, in the form of its disodium salt, is used as a flavor intensifier. There are no known reports bearing on the use of these compounds to reduce gastric side effects of non-steroidal antiinflammatory agents or to reduce the effects of ulcers under any circumstances. The aluminum salts of either N-acetyl-L-glutamine or N-acetyl-L-carnosine [N-(N-acetyl-beta-alanyl)-L-histidine], but not N-acetyl-L-carnosine or L-carnosine per se, have been reported to prevent the exacerbation of gastric ulcers in rats by certain antiinflammatory agents [Tanaka et al., Japan. J. Pharmacol., v. 32, pp. 307-313 (1982); Kunimi et al., loc. cit., pp. 469-477 (1982)]. On the other hand, certain amino acids, including methionine, have been reported to inhibit gastrointestinal ulcers induced by the subcutaneous injection of indomethacin [Urishidani et al., Japan. J. Pharmacol. 27, pp. 316-319 (1977)] and to have a beneficial effect on the gastric mucosal damage of aspirin solutions in rats [Lim et al., J. Pharm. Sci. 68, pp. 295-298 (1979)].